The Web Tables below are excerpts from Resource 2 below, 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure – Web Addenda [Full Text PDF -you may need t register for a free ESC account to access this resource]. Other text and tables are from Resource 1 below:

7.2.3 Mineralocorticoid/aldosterone receptor antagonists

MRAs (spironolactone and eplerenone) block receptors that bind aldosterone and, with different degrees of affinity, other steroid hormone (e.g. corticosteroids, androgens) receptors. Spironolactone or eplerenone are recommended in all symptomatic patients (despite treatment with an ACEI and a beta-blocker) with HFrEF and LVEF ≤35%, to reduce mortality and HF hospitalization.[174, 175]

Caution should be exercised when MRAs are used in patients with impaired renal function and in those with serum potassium levels >5.0 mmol/L. Regular checks of serum potassium levels and renal function should be performed according to clinical status.

7.3.1 Diuretics

Diuretics are recommended to reduce the signs and symptoms of congestion in patients with HFrEF, but their effects on mortality and morbidity have not been studied in RCTs. A Cochrane meta-analysis has shown that in patients with chronic HF, loop and thiazide diuretics appear to reduce the risk of death and worsening HF compared with placebo, and compared with an active control, diuretics appear to improve exercise capacity.[178, 179]

Loop diuretics produce a more intense and shorter diuresis than thiazides, although they act synergistically and the combination may be used to treat resistant oedema. However, adverse effects are more likely and these combinations should only be used with care. The aim of diuretic therapy is to achieve and maintain euvolaemia with the lowest achievable dose. The dose of the diuretic must be adjusted according to the individual needs over time. In selected asymptomatic euvolaemic/hypovolaemic patients, the use of a diuretic drug might be (temporarily) discontinued. Patients can be trained to self-adjust their diuretic dose based on monitoring of symptoms/signs of congestion and daily weight measurements.

Doses of diuretics commonly used to treat HF are provided in Table7.3. Practical guidance on how to use diuretics is given in Web Table 7.7.

For details on the use of the medicines discussed in the following table please see:

However, the document notes that there are safety concerns about this medicine related to hypotension and angioedema. However, the most worrisome issue to me is:

There are additional concerns about its effects on the degradation of beta-amyloid peptide in the brain, which could theoretically accelerate amyloid deposition.189 – 191 However, a recent small14-day study with healthy subjects showed elevation of the beta-amyloid protein in the soluble rather than the aggregable form, which if conﬁrmed over longer time periods in patientswith HFrEF may indicate the cerebral safety of sacubitril/valsartan.192 Long-term safety needs to be addressed.

The above concern is very worrisome to me. And that concern is not addressed in the document in terms of the risk reduction benefit of sacubitril/valsartan.

2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure states:

the ARNI [meaning sacubitril/valsartan] reduced the composite endpoint of cardiovascular death or HF hospitalization significantly, by 20% (138). The benefit was seen to a similar extent for both death and HF hospitalization and was consistent across subgroups. The use of ARNI is associated with the risk of hypotension and renal insufficiency and may lead to angioedema, as well.

EMA,whichsuggestedthat beneﬁtsarethoughttooutweighrisks only in a select group of patients with HFrEF in whom other treat-entsare unsuitable.Therefore,ARBs areindicatedforthetreatmentofHFrEFonlyinpatientswhocannottolerateanACEI becauseofserioussideeffects.ThecombinationofACEI/ARB shouldberestrictedtosymptomaticHFrEFpatientsreceivinga beta-blockerwhoare unabletotolerateanMRA,andmust be used understrict supervision

providedinSection 10.1.Similarly, there is noevidenceon the beneﬁts of antiplatelet drugs(includingacetylsalicylicacid)inpatientswithHFwithoutaccompanying CAD, whereas there is asubstantial risk ofgastro-intestinalbleeding,particularlyinelderly subjects,relatedwith this treatment.

Resources

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. [PubMed Citation] [Full Text HTML] [Full Text PDF]. Eur J Heart Fail. 2016 Aug;18(8):891-975. doi: 10.1002/ejhf.592. Epub 2016 May 20.